Human Gene Module / Chromosome 16 / SEZ6L2

SEZ6L2SEZ6L2 seizure related 6 homolog (mouse)-like 2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
5 / 7
Rare Variants / Common Variants
10 / 1
Aliases
SEZ6L2, PSK-1,  FLJ90517,  SEZ6L2
Associated Syndromes
-
Chromosome Band
16p11.2
Associated Disorders
-
Relevance to Autism

Several studies have found rare variants and genetic association of the SEZ6L2 gene with autism (e.g. Kumar et al., 2009).

Molecular Function

transmembrane receptor, may contribute to specialized endoplasmic reticulum functions in neurons

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to SEZ6L2 (7 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain-specific receptor-like protein family Miyazaki T , et al. (2006) No -
2 Support Recurrent 16p11.2 microdeletions in autism Kumar RA , et al. (2007) Yes -
3 Support Association between microdeletion and microduplication at 16p11.2 and autism Weiss LA , et al. (2008) Yes -
4 Primary Association and mutation analyses of 16p11.2 autism candidate genes Kumar RA , et al. (2009) Yes -
5 Recent Recommendation Genome-wide association study of anthropometric traits in Korcula Island, Croatia Polasek O , et al. (2009) No -
6 Support Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Lim ET , et al. (2017) Yes -
7 Support - Zhou X et al. (2022) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss - - - 18156158 Kumar RA , et al. (2007)
- - copy_number_gain - - - 18184952 Weiss LA , et al. (2008)
- - copy_number_loss - - - 18184952 Weiss LA , et al. (2008)
- - copy_number_gain Familial Maternal - 18156158 Kumar RA , et al. (2007)
c.2446G>A p.Gly816Ser missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.2672C>T p.Ser891Leu missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1185C>T p.Phe395= synonymous_variant De novo - - 28714951 Lim ET , et al. (2017)
c.88C>G p.Leu30Val missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2648C>T p.Ser883Phe missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1785G>A p.Gln595%3D synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.1157G>A p.Arg386His missense_variant - - - 19242545 Kumar RA , et al. (2009)
SFARI Gene score
2

Strong Candidate

SEZ6L2 lies within the 16p11.2 deletion/duplication region. This region is frequently deleted or duplicated in individuals with autism spectrum disorder, developmental delays or intellectual disability. One association study has been performed, showing significant association between autism and a coding variant in SEZ6L2, but this associated failed to replicate.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

SEZ6L2 lies within the 16p11.2 deletion/duplication region. This region is frequently deleted or duplicated in individuals with autism spectrum disorder, developmental delays or intellectual disability. One association study has been performed, showing significant association between autism and a coding variant in SEZ6L2, but this associated failed to replicate.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

SEZ6L2 lies within the 16p11.2 deletion/duplication region. This region is frequently deleted or duplicated in individuals with autism spectrum disorder, developmental delays or intellectual disability. One association study has been performed, showing significant association between autism and a coding variant in SEZ6L2, but this associated failed to replicate.

Reports Added
[New Scoring Scheme]
7/1/2017
4
icon
4

Decreased from 4 to 4

Description

SEZ6L2 lies within the 16p11.2 deletion/duplication region. This region is frequently deleted or duplicated in individuals with autism spectrum disorder, developmental delays or intellectual disability. One association study has been performed, showing significant association between autism and a coding variant in SEZ6L2, but this associated failed to replicate.

Reports Added
[Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.2017]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

SEZ6L2 lies within the 16p11.2 deletion/duplication region. This region is frequently deleted or duplicated in individuals with autism spectrum disorder, developmental delays or intellectual disability. One association study has been performed, showing significant association between autism and a coding variant in SEZ6L2, but this associated failed to replicate.

4/1/2014
No data
icon
4

Increased from No data to 4

Description

SEZ6L2 lies within the 16p11.2 deletion/duplication region. This region is frequently deleted or duplicated in individuals with autism spectrum disorder, developmental delays or intellectual disability. One association study has been performed, showing significant association between autism and a coding variant in SEZ6L2, but this associated failed to replicate.

Krishnan Probability Score

Score 0.56961009453587

Ranking 1018/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.13015316038111

Ranking 7567/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.9417705969989

Ranking 15056/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 6

Ranking 268/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.23078065950895

Ranking 3765/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
CNVs associated with SEZ6L2(1 CNVs)
Sort By:
16p11.2 139 Deletion-Duplication 206  /  1636
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
FCN1 Ficolin-1 Human Protein Binding 2219 O00602
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